Evaluation of Immune Responses to Seasonal Influenza Vaccination in Healthy Volunteers and in Patients After Stem Cell Transplantation

Avetisyan, Gayane; Aschan, J; Hassan, Manal M.; Ljungman, Per

doi:10.1097/tp.0b013e3181772a75

Cited by 80 publications

(72 citation statements)

References 35 publications

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“…7,[21][22][23]25,34,35 Our results confirm that this remains the case even when more potent adjuvanted vaccines are used. Furthermore, we confirm that the type of conditioning has little impact.…”

Section: Discussionsupporting

confidence: 76%

“…21,23,25 Various strategies to enhance influenza vaccine immunogenicity have been reported. 25,28 The potential impact of a 2-dose schedule in HSCT recipients has been controversial.…”

Section: Discussionmentioning

confidence: 99%

“…[21][22][23][24][25] However, these were often limited by their small size and confounded by heterogeneous baseline influenza immunity, with pre-vaccination seroprotection rates ranging from 12% to 92%. 21,[23][24][25] Also, vaccine…”

Section: Discussionmentioning

confidence: 99%

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Graft-versus-host disease is the major determinant of humoral responses to the AS03-adjuvanted influenza A/09/H1N1 vaccine in allogeneic hematopoietic stem cell transplant recipients

Mohty

Bel²,

Vukicevic³

et al. 2011

Haematologica

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BackgroundResponses to influenza vaccines are poorly characterized in immunocompromised patients. The goal of this study was to assess the efficacy of the AS03-adjuvanted influenza H1N1/A/09 vaccine in allogeneic hematopoietic stem cell transplant recipients. Design and MethodsWe enrolled 65 patients and 138 controls in an open prospective study. Controls received one dose and patients 2 doses of the AS03-adjuvanted influenza H1N1/A/09 vaccine at a 3-week interval. Geometric mean titers and seroprotection/seroconversion rates were determined by hemagglutination inhibition before and four weeks after the last immunization. Clinical and biological markers, including immunoglobulins, CD3 + , CD4 + , CD8+ and naïve CD4 + T-cell counts were assessed in all patients. ResultsBaseline seroprotection rates were low in patients (6.6%) and controls (14.8%). After 2 doses, patients (n=57, 92.3%) achieved similar seroprotection rates (84% vs. 87%, P=0.65) and antibody titers (305 vs. 340, P=0.88) as controls (n=131, 93.9%) after one dose. In univariate analysis, transplant-to-vaccination interval less than 12 months, active graft-versus-host disease, immunosuppressive drugs, hemoglobin less than 12g/L, lymphopenia less than1G/L, IgG less than 4g/L, IgA less than 0.5g/L, IgM less than 0.5g/L and naive CD4 + T cells less than 150/mL were significantly associated with weaker responses. Multivariate analysis identified transplant-to-vaccination interval and active graft-versus-host disease as the most powerful negative predictors of antibody responses (P=0.04 and P=0.002, respectively). Vaccination was well tolerated in both cohorts. ConclusionsIn allogeneic hematopoietic stem cell transplant recipients, 2 doses of an adjuvanted influenza vaccine elicited comparable responses to a single dose in healthy individuals. However, vaccine responses remained poor in patients with ongoing graft-versus-host disease, supporting the need for additional strategies in this high-risk patient population. Graft-versus-host disease is the major determinant of humoral responses to the AS03-adjuvanted influenza A/09/H1N1 vaccine in allogeneic hematopoietic stem cell transplant recipients

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Section: Discussionsupporting

confidence: 76%

“…21,23,25 Various strategies to enhance influenza vaccine immunogenicity have been reported. 25,28 The potential impact of a 2-dose schedule in HSCT recipients has been controversial.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Graft-versus-host disease is the major determinant of humoral responses to the AS03-adjuvanted influenza A/09/H1N1 vaccine in allogeneic hematopoietic stem cell transplant recipients

Mohty

Bel²,

Vukicevic³

et al. 2011

Haematologica

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“…The experiences demonstrate that by taking all available measures it might be possible to 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 prevent even patients highly susceptible to any kind of infection from epidemic fatalities Apart from the fact that the effectiveness of vaccination needs to be evaluated by verifying immune responses on the laboratory scale the application of vaccines with adjuvant formulation primarily does not seem to have any adverse immune stimulating effects. 3,4 Therefore, besides common reasonable precautions active vaccination of allogeneic HSCT recipients may provide a safe strategy to conquer new healthcare challenges.…”

Section: To Cite This Versionmentioning

confidence: 99%

H1N1 in allogeneic stem cell recipients: courses of infection and influence of vaccination on graft-versus-host-disease (GVHD)

2010

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“…[34][35][36] In our study, three patients had H1N1 infection despite having been vaccinated. In Only one patient has been tested for H275Y mutation in this study.…”

Section: Discussionmentioning

confidence: 99%

Clinical features and outcome of 2009-influenza A (H1N1) after allogeneic hematopoietic SCT

Mohty

Thomas

Vukicevic

et al. 2011

Bone Marrow Transplant

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The impact of the 2009 H1N1-Influenza A (H1N1) pandemic in allogeneic hematopoietic SCT recipients (allo-HSCT) is not yet well defined. Between May 2009 and May 2010, all allo-HSCTs who presented with respiratory symptoms were screened for the presence of the H1N1 virus. Oseltamivir resistance was assessed and chart reviews were performed for all cases. In all, 51 of 248 (20%) allo-HSCT recipients followed at our outpatient clinic were screened. We identified 10 patients with H1N1 infection. Close contact with children was the most commonly suspected mode of transmission. Upper and lower respiratory tract infections were present in eight and five patients, respectively. Lymphopenia (o1 G/L) was the most frequent biological abnormality. High immunosuppression was responsible for severe infection requiring mechanical ventilation associated with prolonged viral shedding in three patients who had significant comorbidities and GvHD. Two of them developed an oseltamivirresistant strain and both patients died subsequently despite intensive therapy, resulting in a case fatality rate of 20%. In conclusion, although most allo-HSCTs had mild symptoms from H1N1 infection, severe immunosuppression and emergence of oseltamivir resistance were likely responsible for a substantial morbidity, further supporting the need for vaccination and monitoring of close contacts, especially children.

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Evaluation of Immune Responses to Seasonal Influenza Vaccination in Healthy Volunteers and in Patients After Stem Cell Transplantation

Abstract: Seasonal vaccination against influenza boosts the cellular immune response both in SCT patients and healthy controls. The protective effect is lower in the patients in general and especially on those, vaccinated early after SCT.

Cited by 80 publications

References 35 publications

Graft-versus-host disease is the major determinant of humoral responses to the AS03-adjuvanted influenza A/09/H1N1 vaccine in allogeneic hematopoietic stem cell transplant recipients

Graft-versus-host disease is the major determinant of humoral responses to the AS03-adjuvanted influenza A/09/H1N1 vaccine in allogeneic hematopoietic stem cell transplant recipients

H1N1 in allogeneic stem cell recipients: courses of infection and influence of vaccination on graft-versus-host-disease (GVHD)

Clinical features and outcome of 2009-influenza A (H1N1) after allogeneic hematopoietic SCT

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